FDA Approves Oral CGRP Inhibitor Atogepant for Prevention of Episodic Migraine

The oral calcitonin-gene-related peptide (CGRP) peptide inhibitor atogepant (Qulipta, AbbVie) received FDA approval this week for the preventive treatment of episodic migraine headache in adults, according to a company press release.

In the pivotal phase 3 ADVANCE study of atogepant, mean monthly migraine days were significantly reduced vs placebo as early as weeks 1 through 4 among approximately 2000 patients who experienced between 4 and 14 migraine days per month. The FDA approval is based on the full atogepant clinical program that evaluated the safety, efficacy, and tolerability of the CGRP inhibitor which is taken daily to prevent migraine.

Atogepant is the only oral CGRP inhibitor specifically developed for the preventive treatment of migraine.

"This approval reflects a broader shift in the treatment and management paradigm for the migraine community,” said Peter J. Goadsby, MD, PhD, DSc, a neurologist and professor at UCLA and King's College, London, in the company statement. "QULIPTA provides a simple oral treatment option specifically developed to prevent migraine attacks and target CGRP, which is believed to be crucially involved in migraine in many patients." Goadsby is a coauthor of the ADVANCE study and widely recognized for his research on the role of CGRP in migraine etiology.

ADVANCE investigators randomized adults with 4 to 14 migraine days per month in a 1:1:1:1 ratio to receive a once-daily dose of oral atogepant (10 mg, 30 mg, or 60 mg) or placebo for 12 weeks. The primary end point was change from baseline in the mean number of migraine days per month across the 12 weeks.

Results showed statistically significantly greater decreases in mean monthly y migraine days among atogepant vs placebo recipients (3.7 days [10 mg], 3.9 days [30 mg], and 4.2 days [60 mg] vs 2.5 days with placebo; P<.001). A key secondary endpoint—reduction of at least 50% in the 3-month average of migraine days/month—was achieved by a greater proportion of patients treated with any dose of atogepant (10mg/30mg/60mg) over the 12-week treatment period vs placebo (56%/59%/61%, respectively, vs 29%; P<.001).

Results from a pivotal phase 2b/3 trial in the atogepant clinical program demonstrated that treatment with atogepant across all doses and dosing regimens resulted in significantly greater reductions in mean monthly migraine days vs placebo. All 3 atogepant doses also met this trial’s secondary efficacy endpoint of change from baseline in mean monthly headache days.

"I'm particularly encouraged by the convenience of the oral daily use of QULIPTA, its rapid onset of significant efficacy, and its safety and tolerability as well as its high patient response rates,” concluded Goadsby in the statement. “This is a milestone in preventive migraine treatment that I hope will help many patients for years to come."

Nausea, constipation, and fatigue were reported to be the most common adverse reactions associated with treatment and/or discontinuation.

Atogepant will be supplied as 10mg, 30mg, and 60mg tablets in 30-count bottles and is expected to be available in early October 2021, according to AbbVie.